Currently, peptide drugs such as insulin, glucagon and growth hormone, are administered by injection since other routes of administration are ineffective. Previous attempts to improve insulin delivery via the nasal route have shown that ionic detergents and bile salt derivatives can increase the systemic absorption of insulin, but these reagents cause irritation of the nasal mucosa when used on a regular basis. Results from the Diabetes Control and Complications Trial (DCCT) have confirmed that meticulous basis. Results from the Diabetes Control and Complications Trial (DCCT) have confirmed that meticulous management of blood D-glucose levels can significantly reduce the rate of progression and severity of retinal, renal and neural damage among diabetic patients. Availability of nosedrops containing insulin could improve patient comfort and compliance, especially at lunch and dinner time. Research in the laboratory of the Principal Investigator has shown that the commercially available alkylglycosides (tetradecylmaltoside, triclecylmaltoside, dodecylmaltoside and dodecylsucrose) cause an increase in the systemic absorption of insulin applied nasally and a structure/function relationship has emerged with the members of this chemical family. Generally, longer more hydrophobic alkyglycosides tend to be more effective at enhancing systemic insulin absorption following nasal delivery. In this project, we propose to synthesize several additional alkylglycosides, i.e. tridecytsucrose, tetradecytsucrose and hexadecyclmaltoside, which will be tested for their ability to enhance systemic insulin absorption following nasal administration to rats. These preclinical studies are designed to show that alkylglycosides can be used to deliver insulin via the nasal route without producing local irritation or systemic toxicity and to identify one or two lead compounds to take into clinical trials. PROPOSED COMMERCIAL APPLICATION: The potential market for a safe, effective nasal formulation of insulin is very large due to the large number of persons with Type I diabetes melitus. Moreover, if the alkylglycosides can be developed as efficacious, non-toxic excipients for insulin, there are numerous other peptide drugs, in addition to insulin, which could be delivered nasally in the presence of the alkylglycosides. Our long-term goal is to bring a safe and effective nasal insulin formulation to market and to test the same formulation with other peptide drugs.